Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
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Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\n
Thank you all for being part of the journey. 5,000 times thank you!
\\n\\n
Now with 5,000 titles available Open Access, which one will you read next?
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
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"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
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Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\n\n
Thank you all for being part of the journey. 5,000 times thank you!
\n\n
Now with 5,000 titles available Open Access, which one will you read next?
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6082",leadTitle:null,fullTitle:"Advanced Chemical Kinetics",title:"Advanced Chemical Kinetics",subtitle:null,reviewType:"peer-reviewed",abstract:'The book on Advanced Chemical Kinetics gives insight into different aspects of chemical reactions both at the bulk and nanoscale level and covers topics from basic to high class. This book has been divided into three sections: (i) "Kinetics Modeling and Mechanism," (ii) "Kinetics of Nanomaterials," and (iii) "Kinetics Techniques." The first section consists of six chapters with a variety of topics like activation energy and complexity of chemical reactions; the measurement of reaction routes; mathematical modeling analysis and simulation of enzyme kinetics; mechanisms of homogeneous charge compression ignition combustion for the fuels; photophysical processes and photochemical changes; the mechanism of hydroxyl radical, hydrate electron, and hydrogen atom; and acceptorless alcohol dehydrogenation. The understanding of the kinetics of nanomaterials, to bridge the knowledge gap, is presented in the second section. The third section highlights an overview of experimental techniques used to study the mechanism of reactions.',isbn:"978-953-51-3816-7",printIsbn:"978-953-51-3815-0",pdfIsbn:"978-953-51-4031-3",doi:"10.5772/68089",price:119,priceEur:129,priceUsd:155,slug:"advanced-chemical-kinetics",numberOfPages:224,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"d96d5f701addf76fa71abff142b8574a",bookSignature:"Muhammad Akhyar Farrukh",publishedDate:"February 21st 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6082.jpg",numberOfDownloads:17294,numberOfWosCitations:25,numberOfCrossrefCitations:21,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:38,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:84,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 6th 2017",dateEndSecondStepPublish:"March 27th 2017",dateEndThirdStepPublish:"June 23rd 2017",dateEndFourthStepPublish:"September 21st 2017",dateEndFifthStepPublish:"November 20th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"63182",title:"Dr.",name:"Muhammad Akhyar",middleName:null,surname:"Farrukh",slug:"muhammad-akhyar-farrukh",fullName:"Muhammad Akhyar Farrukh",profilePictureURL:"https://mts.intechopen.com/storage/users/63182/images/system/63182.png",biography:"Dr. Muhammad Akhyar Farrukh is serving as an associate professor of chemistry at Forman Christian College (a chartered university), Pakistan. He has been duly awarded three gold medals for his outstanding academic performance in Chemistry and five gold medals including those from Minister HED and Governor of Punjab for his excellent performance in research and service to society. He has been awarded many international and national awards including the Representative of Pakistan award from UNESCO in Morocco, Young Chemist Award from IUPAC in Italy, Young Scientist Award from TWAS in Egypt and IAP/GYA in Germany, Young Scientist Award from IAP/World Economic Forum in China, Young Researcher Award from the Council for Lindau Nobel Laureate Meetings, IUPAC-2015 Award for Chemists as an outstanding chemist from developing countries in South Korea, Research Productivity Award in categories A, B, and C, Productive Scientist of Pakistan award, ranked 11th in Pakistan in the Chemistry category, Young Scientist award in 2017 and 2018, and the SATHA Innovation Award 2018 along with the Gold Medal. He has published +110 papers in international/national reputable journals, published/edited 25 books, issued 7 US patents/applications, presented 49 papers in international/national conferences, and gave 60 plenary/invited lectures in 25 countries around the globe. He has won 2 industrial projects and 6 major Research Grants from TWAS, USM, HEC, PSF, and ORIC GCU in the area of nanotechnology. He established a Nano-Chemistry Lab, and at GC University Lahore, he has supervised 57 M.Phil./Ph.D. theses.",institutionString:"Forman Christian College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Forman Christian College",institutionURL:null,country:{name:"Pakistan"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"503",title:"Chemical Kinetics",slug:"chemical-kinetics"}],chapters:[{id:"56807",title:"Complex Reactions and Dynamics",doi:"10.5772/intechopen.70502",slug:"complex-reactions-and-dynamics",totalDownloads:2148,totalCrossrefCites:10,totalDimensionsCites:17,hasAltmetrics:0,abstract:"Starting from the general idea of reaction kinetics, their classification, concentrations, and chemical equilibrium, we will focus on their activation energy and complexity arising during the chemical reaction. As in complex and higher-dimensional chemical problems, we need special arrangements, specifically, in the case when a system attains different completion paths or several routes. The stiffness of the system can be removed if we distinctly measure their available reaction routes and get a comparison between them and overall reactions. Secondly, the construction and comparison of the invariant region of the manifold based on the modern decomposition techniques in different available reaction routes allow us to discuss the dynamical properties of the system.",signatures:"Muhammad Shahzad and Faisal Sultan",downloadPdfUrl:"/chapter/pdf-download/56807",previewPdfUrl:"/chapter/pdf-preview/56807",authors:[{id:"206308",title:"Dr.",name:"Muhammad",surname:"Shahzad",slug:"muhammad-shahzad",fullName:"Muhammad Shahzad"}],corrections:null},{id:"57109",title:"Mathematical Modeling and Simulation of Nonlinear Process in Enzyme Kinetics",doi:"10.5772/intechopen.70914",slug:"mathematical-modeling-and-simulation-of-nonlinear-process-in-enzyme-kinetics",totalDownloads:1594,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"A deep and analytical understanding of the enzyme kinetics has attracted a great attention of scientists from biology, medicine, chemistry, and pharmacy. Mathematical models of enzyme kinetics offer several advances for this deep and analytical understanding due to their in compensable potential in predicting kinetic processes and anticipating appropriate interventions when required. This chapter concerns mathematical modeling analysis and simulation of enzyme kinetics. Experimental data and available knowledge on enzyme mechanics are used in constituting a mathematical model. The models are either in the form of linear or nonlinear ordinary differential equations or partial differential equations. These equations are composed of kinetic parameters such as kinetic rate constants, initial rates, and concentrations of enzymes. The nonlinear nature of enzymatic reactions and a large number of parameters have caused major issues with regard to efficient simulation of those reactions. In this work, an enzymatic system that includes Michaelis-Menten and Ping Pong kinetics is modeled in the form of differential equations. These equations are solved numerically in which the system parameters are estimated. The numerical results are compared with the results from an existing work in literature.",signatures:"Lakshmanan Rajendran, Mohan Chitra Devi, Carlos Fernandez and\nQiuming Peng",downloadPdfUrl:"/chapter/pdf-download/57109",previewPdfUrl:"/chapter/pdf-preview/57109",authors:[{id:"35190",title:"Prof.",name:"Lakshmanan",surname:"Rajendran",slug:"lakshmanan-rajendran",fullName:"Lakshmanan Rajendran"},{id:"207726",title:"Dr.",name:"Carlos",surname:"Fernandez",slug:"carlos-fernandez",fullName:"Carlos Fernandez"},{id:"220050",title:"Ms.",name:"Chitra Devi",surname:"Mohan",slug:"chitra-devi-mohan",fullName:"Chitra Devi Mohan"},{id:"225046",title:"Prof.",name:"Qiuming",surname:"Peng",slug:"qiuming-peng",fullName:"Qiuming Peng"}],corrections:null},{id:"56917",title:"Autoignition and Chemical-Kinetic Mechanisms of Homogeneous Charge Compression Ignition Combustion for the Fuels with Various Autoignition Reactivity",doi:"10.5772/intechopen.70541",slug:"autoignition-and-chemical-kinetic-mechanisms-of-homogeneous-charge-compression-ignition-combustion-f",totalDownloads:1718,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This work demonstrates the autoignition and chemical-kinetic mechanisms of homogeneous charge compression ignition (HCCI) combustion for the fuels with various autoignition reactivity. This is done for four fuels: methane, dimethyl ether (DME), iso-octane and n-heptane. Methane and iso-octane are selected as the single-stage ignition fuel, and DME and n-heptane are selected as the two-stage ignition fuel. As a tool for understanding the characteristics of autoignition and combustion process in HCCI engine, a zero-dimensional single-zone engine model of ‘CHEMKIN’ in Chemkin-Pro was used. The complete compression and expansion strokes were modeled using an engine with a connecting-rod length to crank-radius ratio of 3.5 and a compression ratio of 13. A detailed chemical-kinetic mechanism for methane and DME is Mech_56.54 (113 species and 710 reactions). For iso-octane and n-heptane, a detailed chemical-kinetic mechanism from Lawrence Livermore National Laboratory (1034 species and 4236 reactions) is used. The results show that methane and iso-octane exhibit only the main heat release, ‘high-temperature heat release (HTHR)’ by high-temperature reactions (HTR). In contrast, both DME and n-heptane exhibit the first heat release ‘low-temperature heat release (LTHR)’ associated with low-temperature reactions (LTR) before HTHR.",signatures:"Dongwon Jung",downloadPdfUrl:"/chapter/pdf-download/56917",previewPdfUrl:"/chapter/pdf-preview/56917",authors:[{id:"207505",title:"Dr.",name:"Dongwon",surname:"Jung",slug:"dongwon-jung",fullName:"Dongwon Jung"}],corrections:null},{id:"56771",title:"New Materials to Solve Energy Issues through Photochemical and Photophysical Processes: The Kinetics Involved",doi:"10.5772/intechopen.70467",slug:"new-materials-to-solve-energy-issues-through-photochemical-and-photophysical-processes-the-kinetics-",totalDownloads:1584,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Kinetic rates of energy production are extremely controlled by the competing processes that occur in systems capable of energy transfer. Besides organic and inorganic compounds already known as electronically actives, supramolecular systems can be thought to form energy transfer complexes to efficiently convert, for instance, light into electricity and the mechanisms for that can be of any kind. Photophysical and photochemical processes can simultaneously occur in such systems to provide energy conversion, by competing mechanisms or collaborative ones. Thus, to investigate the kinetic rates of each process and to understand the dynamics of the electronic excited states population and depopulation in strategically structured materials, can offer important tools to efficiently make use of this not always so evident power of supramolecular materials. In this chapter, we present the state-of-the-art of the use of photophysical processes and photochemical changes, presented by new materials and devices to provide a control of energy transfer processes and enable distinct applications, since energy conversion to sensing and imaging techniques to material characterization.",signatures:"Tatiana Duque Martins, Antonio Carlos Chaves Ribeiro, Geovany\nAlbino de Souza, Diericon de Sousa Cordeiro, Ramon Miranda Silva,\nFlavio Colmati, Roberto Batista de Lima, Lucas Fernandes Aguiar,\nLeandro Lima Carvalho, Renan Gustavo Coelho S. dos Reis and\nWemerson Daniel C. dos Santos",downloadPdfUrl:"/chapter/pdf-download/56771",previewPdfUrl:"/chapter/pdf-preview/56771",authors:[{id:"35340",title:"Prof.",name:"Tatiana",surname:"Martins",slug:"tatiana-martins",fullName:"Tatiana Martins"},{id:"165059",title:"MSc.",name:"Antonio Carlos",surname:"Ribeiro",slug:"antonio-carlos-ribeiro",fullName:"Antonio Carlos Ribeiro"},{id:"174142",title:"M.Sc.",name:"Diericon",surname:"Cordeiro",slug:"diericon-cordeiro",fullName:"Diericon Cordeiro"},{id:"175556",title:"Dr.",name:"Flavio",surname:"Colmati",slug:"flavio-colmati",fullName:"Flavio Colmati"},{id:"208947",title:"BSc.",name:"Ramon",surname:"Miranda",slug:"ramon-miranda",fullName:"Ramon Miranda"},{id:"208948",title:"BSc.",name:"Lucas",surname:"Aguiar",slug:"lucas-aguiar",fullName:"Lucas Aguiar"},{id:"217360",title:"Dr.",name:"Leandro",surname:"Carvalho",slug:"leandro-carvalho",fullName:"Leandro Carvalho"},{id:"217361",title:"MSc.",name:"Renan",surname:"Reis",slug:"renan-reis",fullName:"Renan Reis"},{id:"217362",title:"Mr.",name:"Wemerson",surname:"Santos",slug:"wemerson-santos",fullName:"Wemerson Santos"},{id:"217363",title:"Prof.",name:"Roberto",surname:"Lima",slug:"roberto-lima",fullName:"Roberto Lima"},{id:"243996",title:"Mr.",name:"Geovany Albino",surname:"De Souza",slug:"geovany-albino-de-souza",fullName:"Geovany Albino De Souza"}],corrections:null},{id:"56740",title:"Competition Kinetics: An Experimental Approach",doi:"10.5772/intechopen.70483",slug:"competition-kinetics-an-experimental-approach",totalDownloads:1547,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"In this chapter, free radical kinetics with the help of competition kinetics and some experimental results calculated by competition kinetics to find out the rate constant of reactive species (●OH, eaq−, ●H) with target compound, which is used by radiation chemists is briefly discussed. The competition kinetics method is well validated by taking ciprofloxacin, norfloxacin and bezafibrate as example compounds. The bimolecular rate constants of hydroxyl radical, hydrate electron and hydrogen atom has been calculated for example solute species (ciprofloxacin, norfloxacin and bezafibrate).",signatures:"Murtaza Sayed, Luqman Ali Shah, Javed Ali Khan, Noor S. Shah,\nRozina Khattak and Hasan M. Khan",downloadPdfUrl:"/chapter/pdf-download/56740",previewPdfUrl:"/chapter/pdf-preview/56740",authors:[{id:"207213",title:"Prof.",name:"Rozina",surname:"Khattak",slug:"rozina-khattak",fullName:"Rozina Khattak"},{id:"207652",title:"Dr.",name:"Murtaza",surname:"Sayed",slug:"murtaza-sayed",fullName:"Murtaza Sayed"},{id:"214471",title:"Dr.",name:"Javed",surname:"Khan",slug:"javed-khan",fullName:"Javed Khan"},{id:"214472",title:"Dr.",name:"Noor Samad",surname:"Shah",slug:"noor-samad-shah",fullName:"Noor Samad Shah"},{id:"214473",title:"Dr.",name:"Hasan",surname:"Khan",slug:"hasan-khan",fullName:"Hasan Khan"},{id:"214525",title:"Dr.",name:"Luqman Ali",surname:"Shah",slug:"luqman-ali-shah",fullName:"Luqman Ali Shah"}],corrections:null},{id:"59039",title:"Catalyst Kinetics and Stability in Homogeneous Alcohol Acceptorless Dehydrogenation",doi:"10.5772/intechopen.70654",slug:"catalyst-kinetics-and-stability-in-homogeneous-alcohol-acceptorless-dehydrogenation",totalDownloads:1672,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The anthropogenic climate changes caused by meeting the energy demands of society by use of fossil fuels render the development of benign alternatives imperative. Probably, the most promising alternative is generating energy by means of power units driven by, e.g., solar, wind, water, etc., and then storing the energy that is not immediately used in battery type devices. Such a device might consist of hydrogen chemically stored as alcohol(s). The advantage of this method is that it allows gaseous hydrogen to be stored much more efficiently when liquefied as an alcohol. Moreover, as will be shown in this review, it is possible to release the hydrogen under mild conditions when employing homogeneous catalysis. This review considers the kinetic aspects of homogeneously catalysed acceptorless alcohol dehydrogenation reactions. For clarity, the sections are divided according to alcohol substrate, and each metal are described and discussed in subsections. Moreover, the kinetic information in the homogeneously catalysed AAD is traditionally provided simply as the turnover frequency, and more in-depth studies on the actual kinetic parameters are to date still largely elusive.",signatures:"Martin Nielsen",downloadPdfUrl:"/chapter/pdf-download/59039",previewPdfUrl:"/chapter/pdf-preview/59039",authors:[{id:"207946",title:"Dr.",name:"Martin",surname:"Nielsen",slug:"martin-nielsen",fullName:"Martin Nielsen"}],corrections:null},{id:"56747",title:"Oxidation of Glycerol to Lactic Acid by Gold on Acidified Alumina: A Kinetic and DFT Case Study",doi:"10.5772/intechopen.70485",slug:"oxidation-of-glycerol-to-lactic-acid-by-gold-on-acidified-alumina-a-kinetic-and-dft-case-study",totalDownloads:1445,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The aim of this chapter is to present proposed kinetic and density functional theory (DFT) models for the selective oxidation of glycerol to various hydroxy-acids over an acidified Au/γ-Al2O3 catalyst. Glycerol oxidation over gold-based catalysts to value-added chemicals continues to attract attention worldwide. Both the kinetics and theoretical mechanisms of this reaction have been reported in the past. However, some of the reported kinetic data was possibly collected under mass transfer limitations. In this case study we demonstrate that if mass transfer is eliminated, a pseudo zero-order model can be fitted to the experimental data with a high degree of correlation. Furthermore, we propose a plausible mechanism of pyruvaldehyde (PA) isomerisation to lactic acid (LAC) over supported molybdenum Lewis acid sites as investigated with density functional theory (DFT) approach. A proposed DFT model suggested that the rate-limiting step in the isomerisation of PA to LAC, catalysed by a Mo Lewis acid-site, could be the dissociation of a proton from an adsorbed water molecule ? the protonation step.",signatures:"Thabang A. Ntho, Pumeza Gqogqa and James L. Aluha",downloadPdfUrl:"/chapter/pdf-download/56747",previewPdfUrl:"/chapter/pdf-preview/56747",authors:[{id:"183974",title:"Dr.",name:"Thabang",surname:"Ntho",slug:"thabang-ntho",fullName:"Thabang Ntho"},{id:"207736",title:"MSc.",name:"Pumeza Gqogqa",surname:"Gqogqa",slug:"pumeza-gqogqa-gqogqa",fullName:"Pumeza Gqogqa Gqogqa"},{id:"207739",title:"Dr.",name:"James",surname:"Aluha",slug:"james-aluha",fullName:"James Aluha"}],corrections:null},{id:"56768",title:"Hydrothermal Precipitation of β-FeOOH Nanoparticles in Mixed Water/Alcohol Solvent",doi:"10.5772/intechopen.70503",slug:"hydrothermal-precipitation-of-feooh-nanoparticles-in-mixed-water-alcohol-solvent",totalDownloads:1237,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"In this research, synthesis of β-FeOOH nanoparticles was carried out using different alcohol/water mixed solvents. Four different alcohols were mixed with water to form solution of different surface tension. A relationship between particle size and surface tension has been drawn from theoretical analysis. A linear relationship was shown to exist between surface tension and particle size under the reported conditions. Statistically designed experiments were conducted to evaluate the interactions of process parameters on the particle growth. A generic correlation has also been developed empirically to predict particle size.",signatures:"Mahabubur Chowdhury",downloadPdfUrl:"/chapter/pdf-download/56768",previewPdfUrl:"/chapter/pdf-preview/56768",authors:[{id:"178588",title:"Dr.",name:"Mahabubur",surname:"Chowdhury",slug:"mahabubur-chowdhury",fullName:"Mahabubur Chowdhury"}],corrections:null},{id:"56816",title:"Adsorption, Kinetics and Photoactivity of ZnO-Supported Fly Ash-Sepiolite Ternary Catalyst",doi:"10.5772/intechopen.70504",slug:"adsorption-kinetics-and-photoactivity-of-zno-supported-fly-ash-sepiolite-ternary-catalyst",totalDownloads:1374,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Nanocomposites have been attracting more attention in various fields. In this chapter, ZnO-supported fly ash-sepiolite (ZnO-FA-Sep) was prepared as a ternary composite for the evaluation of adsorption capacities and photocatalytic activities. Characterization studies supplied information about the surface morphology variation before and after ZnO loading within the FA-Sep environment. Strong dark adsorption capacities of the supported catalysts improved their photocatalytic performances, in terms of methyl orange (MO) decolorization and degradation processes. This study not only provided important inspirations for developing support materials but also opened new features to facilitate the photocatalyts' performances.",signatures:"Ayşe Neren Ökte",downloadPdfUrl:"/chapter/pdf-download/56816",previewPdfUrl:"/chapter/pdf-preview/56816",authors:[{id:"176470",title:"Prof.",name:"A.Neren",surname:"Ökte",slug:"a.neren-okte",fullName:"A.Neren Ökte"}],corrections:null},{id:"56847",title:"Kinetics of Heterogeneous Self-Propagating High-Temperature Reactions",doi:"10.5772/intechopen.70560",slug:"kinetics-of-heterogeneous-self-propagating-high-temperature-reactions",totalDownloads:1547,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"In this chapter, we present an overview of experimental techniques utilized and kinetic data collected for exothermic self-sustained noncatalytic heterogeneous reactions. The data focuses on five primary experimental techniques: electrothermal explosion, differential thermal analysis, electrothermography, combustion velocity/temperature analyses, and several advanced in situ diagnostics, including time-resolved X-ray diffraction.",signatures:"Christopher E. Shuck and Alexander S. Mukasyan",downloadPdfUrl:"/chapter/pdf-download/56847",previewPdfUrl:"/chapter/pdf-preview/56847",authors:[{id:"21434",title:"Dr.",name:"Alexander S.",surname:"Mukasyan",slug:"alexander-s.-mukasyan",fullName:"Alexander S. Mukasyan"},{id:"215636",title:"Dr.",name:"Christopher",surname:"Shuck",slug:"christopher-shuck",fullName:"Christopher Shuck"}],corrections:null},{id:"56769",title:"Ultrasound as a Metrological Tool for Monitoring Transesterification Kinetics",doi:"10.5772/intechopen.70501",slug:"ultrasound-as-a-metrological-tool-for-monitoring-transesterification-kinetics",totalDownloads:1429,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:0,abstract:"Ultrasound has been widely used as a technological alternative way to analyse non-invasively an assortment of materials. It includes liquids with dissimilar physical characteristics, including mono- and multi-phasic mixtures, suspension formation and dissolution, in-line processing, among other practical applications. Regardless the huge spread of uses, so far ultrasound has not been proved to be able to quantify transesterification kinetics with a metrological approach. The aim of this chapter is to demonstrate that a properly designed ultrasonic experiment can be developed to identify remarkable stages of a transesterification reaction to produce biodiesel. The method was compared both with gas chromatography and hydrogen nuclear magnetic resonance (1H NMR). For an in-line application, ultrasound has been proved to work properly as a monitoring tool for chemical reaction kinetics.",signatures:"Raphaela M. Baêsso, Pâmella A. Oliveira, Gabriel C. Moraes, André\nV. Alvarenga and Rodrigo P.B. Costa-Félix",downloadPdfUrl:"/chapter/pdf-download/56769",previewPdfUrl:"/chapter/pdf-preview/56769",authors:[{id:"111416",title:"Dr.",name:"Rodrigo",surname:"Costa-Félix",slug:"rodrigo-costa-felix",fullName:"Rodrigo Costa-Félix"},{id:"113694",title:"Dr.",name:"Andre",surname:"Alvarenga",slug:"andre-alvarenga",fullName:"Andre Alvarenga"},{id:"207671",title:"MSc.",name:"Raphaela",surname:"Baesso",slug:"raphaela-baesso",fullName:"Raphaela Baesso"},{id:"207672",title:"BSc.",name:"Pamella",surname:"Oliveira",slug:"pamella-oliveira",fullName:"Pamella Oliveira"},{id:"207675",title:"BSc.",name:"Gabriel",surname:"Cataldo",slug:"gabriel-cataldo",fullName:"Gabriel Cataldo"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"2397",title:"Advanced Aspects of 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1. Introduction
Thromboembolic diseases are a leading source of morbidity and death in the United States. Thrombosis can happen in either the arteries or the veins. Acute myocardial infarction (MI), ischemic stroke, and limb gangrene are all caused by arterial thrombosis. Deep vein thrombosis (DVT), which can cause post-thrombotic syndrome, and pulmonary embolism (PE), which can be fatal or cause thromboembolic pulmonary hypertension, are both examples of venous thromboembolism (VTE). Arterial thrombosis is usually managed using antiplatelet therapy. On the other hand, VTE episodes are typically managed using anticoagulant therapy [1].
Anticoagulant drugs are the mainstay of therapy for many thrombotic disorders. The selection of one agent over the other is usually guided by balancing the risks versus the benefits of these anticoagulants. Also, it requires deep knowledge and understanding of the clinical pharmacology, efficacy, safety, and clinical outcomes for each of these anticoagulants.
Historically. Jay McLean and William Henry Howell discovered heparin a century ago, in 1914. However, it was first used in clinical practice in the 1940s. It’s given subcutaneously or intravenously, and it binds to antithrombin. This will improve its capacity to inactivate several clotting factors such as thrombin, factor Xa, and factor IXa [2]. Later on, several oral and parenteral antithrombotic agents are used to prevent and treat thrombotic episodes. In 1940, Karl Link and colleagues discovered warfarin which is a vitamin-k antagonist. Warfarin was first marketed as a rodenticide. Later on, it was adopted for therapeutic usage as an anticoagulant [3].
In 2003, the discovery of ximelagatran showed that a particular oral thrombin inhibitor might be safe and effective in a range of thrombotic diseases, paving the way for introducing a new class of anticoagulants [4]. Following these advancements, a major millstone was declared in the field of anticoagulation. Several direct oral anticoagulants (DOACs) targeting factors Xa and II were introduced from 2007 to 2014. According to several landmark randomized studies, they were shown to be equally safe and efficacious as warfarin in preventing and treating venous thromboembolism and stroke prevention in atrial fibrillation. These advancements led to an enormous change in the landscape of managing thrombotic events [5].
This chapter is intended to review the currently available oral anticoagulants, including vitamin K antagonists (VKA), such as warfarin, and the (DOACs) such as dabigatran, apixaban, rivaroxaban, and edoxaban. In addition, it will discuss periprocedural management of anticoagulants, reversal modalities and highlight the major future advancements in the field of anticoagulation.
2. Vitamin K Antagonists
Warfarin is a vitamin K antagonist that was approved by the US Food and Drug Authority (FDA) in 1954 for stroke prevention. It is approved in many other indications such as managing and preventing VTE. Until recently, it was the only oral agent approved for these indications. However, more oral anticoagulants have been approved that possess more advantages and better pharmacokinetic properties. However, warfarin still a widely used medication to prevent blood clotting disorders. Warfarin administration remains a challenge despite being used for more than 60 years. Warfarin has a narrow therapeutic index and monitored regularly using international normalized ratio (INR). Duo to it inter and intra individual variation in response and multiple drug and food interactions, warfarin was replaced as a first line anticoagulant agent [6].
2.1 Mechanism of action
Warfarin exerts it anticoagulant effect by interfering with vitamin K epoxide reductase in the liver which serve as a cofactor for the carboxylation of glutamate to γ-carboxyglutamates. This process leads to the inhibition of vitamin K–dependent γ-carboxylation of factors II, VII, IX, and X. However, Vitamin K antagonist does not inhibit the existing γ-carboxyglutamates that can lead to delay in its anticoagulant effect [6].
2.2 Pharmacology
Warfarin consists of a racemic mixture of S-warfarin and R-warfarin, in which the S- form being more active. It has high bioavailability with rapid absorption from the gastrointestinal tract. After drug administration, warfarin reaches maximum concentration within 90 mins. Warfarin is highly albumin bound with a half-life of 36–42 hours. Warfarin is metabolized mainly in the liver through the cytochrome P450 (CYP) enzymes. However, the two isomers and metabolized through a different pathway in the liver. CYP2C9 is associated with the metabolism of the more potent S-warfarin whereas R-warfarin mainly metabolized by CYP1A2 and CYP3A4 [6].
2.3 Indication and dosing
Warfarin has multiple indications including venous thrombosis, prosthetic heart valves and more commonly arterial fibrillation. Usually, the starting dose for warfarin is 5–10 mg daily. However, lower doses can be initiated for patients at high risk of bleeding. Patients with known genetic polymorphism in CYP2C9 or VKORC1 can be more sensitive to warfarin. Also, elderly patients, patients with chronic kidney disease or patients on other medications that can cause bleeding can be initiated at a lower dose and up titrated to INR goal. Duo to its delayed antithrombotic effect, patients with established clot or high risk for thrombosis are bridged with a fast-acting parenteral anticoagulant. Commonly, heparin or enoxaparin are given concomitantly with warfarin until INR is at goal for 2 consecutive days with a minimum of 5 days on parenteral anticoagulant [6].
2.4 Monitoring
Warfarin is a drug known for its narrow therapeutic index as well as having multiple drug and food interactions. Therefore, continuous monitoring is important to ensure anticoagulation efficacy is achieved and severe side effects are avoided. INR is calculated from prothrombin time which is a test that measures how long a clot is formed in a blood sample is performed when patients are on warfarin. Mostly, warfarin is given to achieve an INR goal of 2–3. However, patients with a mechanical mitral valves or mechanical aortic valve replacement with Starr-Edwards or disc valves have a higher INR target of 2.5–3.5 duo to higher thromboembolic risk [6].
2.5 Side effects
One of the major risks associated with using warfarin is bleeding and the severity of bleeding can vary. Majority of bleeding side effect is seen when INR supratherapeutic. Therefore, INR monitored and maintained at target is essential to minimize bleeding risk. There are several approaches to manage a supratherapeutic INR and the choice usually depends on the present or absent of bleeding, severity of bleeding and magnitude in which INR increased. Skin necrosis is a rare complication associated with warfarin administration in patients with protein C or S deficiency [6].
2.6 Drug interaction
Warfarin can interact with large number of medications. Drugs can cause pharmacodynamic or pharmacokinetic interaction with warfarin. Pharmacokinetic interactions involve medications that inhibit or induce CYP2C9, CYP1A2 or CYP3A4 which can alter warfarin concentration. Inhibitors of the CYP enzymes can interfere with warfarin metabolism that leads to higher warfarin concentration. However, CYP enzyme inducers can increase warfarin removal, therefore, decrease its effect. Pharmacodynamic interaction can occur when warfarin given with other anticoagulants, antiplatelet, non-steroidal anti-inflammatory drugs, or serotonin Reuptake Inhibitors. In which, these drugs can increase risk of bleeding [6].
3. Direct Oral Anticoagulants
Direct oral anticoagulants (DOACs) have been introduced to the market initially in 2010 as a potential alternative for warfarin. They possess many advantages over warfarin that placed them as the first-line anticoagulant option for many indications. These agents include apixaban, rivaroxaban, edoxaban, and dabigatran. All of these agents do not require regular monitoring of their anticoagulant effect and they achieve the target anticoagulation level shortly given their fast onset of action compared to warfarin. These significant advantages placed these agents as the preferred anticoagulant option by patients and clinicians [7].
3.1 Mechanism of action
Factor Xa is a crucial coagulation factor in the coagulation cascade that leads to the formation of thrombin and clot generation. Apixaban, rivaroxaban, and edoxaban, bind directly and reversibly to factor Xa and inhibit its action leading to a strong anticoagulation activity. On the other side, dabigatran inhibits directly factor IIa (thrombin), leading to the prevention of clot formation [8].
3.2 Pharmacology
Apixaban binds directly to factor Xa when free and when thrombin bound. It has a bioavailability of approximately 50% and reaches a plasma peak in about 2 hours with maximum plasma concentration in about 3 to 4 hours. It has a half-life of approximately 12 hours after oral administration necessitating twice-daily dosing. It is metabolized mainly by CYP3A4 and eliminated in both urine and feces. Renal elimination accounts for 27% of total clearance. Apixaban has no interaction with food but is a substrate of P-glycoprotein (P-gp) and CYP3A4 requiring vigilant review of concurrent medications for possible drug–drug interactions [9].
Dabigatran is the active form of the prodrug dabigatran etexilate, which binds thrombin directly and competitively inhibiting its activity. The approximate bioavailability of dabigatran after oral administration is 3–7%, with peak plasma concentration achievement within 2 hours. The bioavailability increased to 75% after the pellets were taken without the capsule. Therefore, the capsules should not be broken, chewed, or opened before administration. The half-life of dabigatran is approximately 12–17 hours, necessitating twice-daily dosing. Dabigatran is mainly eliminated in the urine with a renal clearance of roughly 80%. It is a substrate of P-gp and therefore, it carries a risk for drug–drug interactions [9].
Edoxaban binds selectively to factor Xa and inhibits its action without the need for a cofactor (i.e., antithrombin III). It has a bioavailability of approximately 62% and reaches a peak plasma concentration in about 1 to 2 hours. It has a half-life of approximately 10–14 hours, and 50% of the total clearance is through urine. Therefore, edoxaban blood levels are increased or decreased in patients with poor or good renal function. Edoxaban is a substrate for P-gp and CYP3A4, increasing the risk for drug–drug interactions [9].
Rivaroxaban is a selective inhibitor of factor Xa with no requirement for a cofactor (i.e., antithrombin III) with no direct effect on platelet aggregation. It has a very high bioavailability following oral administration of 2.5 mg and 10 mg doses reaching 80–100%. Administration with food increases the bioavailability of rivaroxaban. Therefore, it should be taken with food. Peak plasma concentration is achieved in about 2 to 4 hours. It has a renal clearance of up to 30%. Rivaroxaban is a substrate for P-gp increasing the risk of drug–drug interactions [9]. Table 1 summarizes the pharmacological properties of DOACs.
Apixaban
Dabigatran
Edoxaban
Rivaroxaban
Mechanism of action
Factor Xa
Thrombin
Factor Xa
Factor Xa
Pro-drug
No
Yes
No
No
Bioavailability
50%
3%-7%
62%
66%-80%
Time to peak
2 hours
2 hours
1-2 hours
2-4 hours
Half-life
12 hours
12-17 hours
12-14 hours
9-13 hours
Protein binding
87%
35%
55%
90%
Renal elimination
27%
80%
50%
30%
Substrate of CYP3A4
Yes
No
Yes
Yes
Substrate of P-gp
Yes
Yes
Yes
Yes
Dialyzable
No
Yes
No
No
Table 1.
Pharmacological properties of DOACs.
3.3 Indications and dosing
DOACs are currently used in different indications, including reducing the incidence of stroke in patients with NVAF, treatment of acute VTE, and reducing the risk of recurrent VTE. Finally, apixaban, rivaroxaban, and dabigatran have been approved by US FDA and European Medical Agency (EMA) for thromboprophylaxis post orthopedic surgeries (i.e., knee and hip replacements). Apixaban and rivaroxaban are approved for post-knee and hip replacement surgeries, and dabigatran is only approved for post-hip replacement surgery. In addition, rivaroxaban is also approved for VTE prophylaxis in acutely ill medical patients at risk for thromboembolic complications, not at high risk of bleeding [9]. Table 2 illustrates the usual dosing recommendations for the various indications.
Apixaban
Dabigatran
Edoxaban
Rivaroxaban
Stroke prevention in nonvalvular atrial fibrillation (NVAF)
5 mg PO BID 2.5 mg PO BID if two of the following occurs:
Age ≥ 80 years
Scr ≥ 1.5 mg/dl
Weight ≤ 60 kg
150 mg PO BID
60 mg PO once daily
Not recommended with CrCl > 95 ml/min
20 mg PO once daily
Treatment of acute venous thromboembolism (VTE)
10 mg PO BID for 7 days, then 5 mg PO BID
Following 5-10 days of initial parenteral therapy: 150 mg PO BID
Following 5-10 days of initial parenteral therapy:
Weight > 60 kg: 60 mg PO once daily
Weight ≤ 60 kg: 30 mg PO once daily
15 mg PO BID for 21 days, then 20 mg PO once daily
Reduction in the risk of recurrent VTE
2.5 mg PO BID
150 mg PO BID
Not approved
10 mg PO once daily
Post-knee/hip replacement DVT prophylaxis
2.5 mg PO BID 12-24 hours post-op
Hip replacement duration: 35 days
Knee replacement duration: 12 days
Hip replacement only: 110 mg PO 1-4 hours post-surgery, then 220 mg PO once daily for 28-35 days
Not approved
10 mg PO once daily 6-10 hours post-op
Hip replacement duration: 35 days
Knee replacement duration: 12 days
VTE prophylaxis in acutely ill medical patients at risk for thromboembolic complications, not at high risk of bleeding
Not approved
Not approved
Not approved
10 mg PO once daily in the hospital and after hospital discharge for a total duration of 31-39 days
Table 2.
DOACs approved indications and recommended doses for normal kidney patients.
3.4 Monitoring
DOACs possess the advantage of having predictable pharmacokinetic and pharmacodynamic properties making their regular monitoring of blood levels or coagulation factors not necessary. This provides a great advantage and more convenience to patients than the traditional anticoagulant warfarin. Currently, there are no validated and clinically feasible tests to measure the anticoagulant effect of DOACs on daily basis. Besides, routine monitoring of kidney function is necessary to ensure appropriate clearance of DOACs as all of them have varying degrees of renal elimination. This becomes of high importance when dealing with end-stage renal disease patients or patients on hemodialysis. Monitoring hepatic function every 6 to 12 months is recommended as all DOACs except dabigatran are metabolized by the liver. Regular follow-up on patient adherence is also encouraged to ensure the safety and efficacy of the anticoagulation given their short duration of action [9].
3.5 Side effects
As with all anticoagulants, the main severe and concerning side effect is bleeding. Careful watching of signs and symptoms of bleeding and proper patient education on identifying them is crucial. Dyspepsia is another reported side effect more linked to dabigatran. Taking dabigatran with food should help with minimizing dyspepsia as the body tolerates the medication with time [10].
3.6 Choosing an anticoagulant agent
Warfarin could be an appealing anticoagulant option in many cases. For example, it could be an adequate option to be sued in patients with an estimated creatinine clearance (CrCl) of less than 30 mL/min as those individuals were excluded from many clinical trials that compared warfarin to the DOACs. Also, it could be used in patients with poor medication adherence. This is mainly because many of the currently available DOACs are dosed to be taken twice daily. This could affect patient adherence. In addition, the presence of laboratory assessment modalities like the INR can identify poor medication adherence. Despite the long list of interacting medications with warfarin, the use of warfarin could be preferred as dose adjustments based on INR monitoring can facilitate titration of the anticoagulant response. Warfarin remains the least expensive anticoagulant currently available. This could make it a reasonable option for individuals who cannot afford the more costly options [11].
DOACs are considered the first line option in many indications given their predicted pharmacokinetics and pharmacodynamics which minimizes the need for regular drug monitoring compared to warfarin. They are dosed either once daily or twice daily and do not have significant drug-food interactions. Patients with various degrees of renal impairment (i.e. CrCL <30 ml/min) were excluded from the DOACs’ pivotal trials, therefore their use in this certain population is debatable. However, apixaban, for example has good pharmacokinetic data supporting its use in hemodialysis (HD) patients as it has very low renal clearance that accounts for only 25%. Currently, apixaban is recommended for stroke prevention in atrial fibrillation patients with end stage renal disease (ESRD) on HD. On the other hand, patients with poor compliance may benefit more from being on warfarin rather than DOACs as the effect of warfarin stays longer than DOACs. If a patient misses one dose of warfarin, the INR would still be in the therapeutic range for one or more days. Finally, the need to monitor kidney function with DOACs still exists and crucial to assess the need for renal dose adjustments [12, 13].
3.7 Periprocedural management of anticoagulation
Management of anticoagulation before and after surgeries such as thrombectomy is very crucial safety step to ensure safe and effective surgical interventions with minimal chances for bleedings. The appropriate knowledge of anticoagulants pharmacokinetics properties and the degree of bleeding risk of the procedure are two essential factors to formulate an appropriate periprocedural anticoagulation plan. Special considerations should be taken with individuals with impaired renal or liver functions [14].
In patients who are on a DOAC and going into a minimal risk procedure, omitting one dose of the anticoagulant on the day of the procedure is sufficient. However, in low or moderate risk procedures, the anticoagulant should be omitted for one day before the procedure and restart one day after the procedure. In high-risk procedures, omitting the DOAC agent two days before and after the procedure would reasonable. Table 3 summarizes the periprocedural management of anticoagulants.
Procedure Bleeding Risk
DOAC
Warfarin
Minimal
Omit anticoagulant on the day of procedure
No interruption needed
Low
Omit anticoagulant one day before the procedure
Reinitiate anticoagulant one day after the procedure
For individuals receiving dabigatran with CrCl 30 to 50 mL/min: omit two days before procedure.
Assess thromboembolic risk:
Low – moderate risk: interrupt 5 days before the procedure without parenteral anticoagulant bridging
High risk: interrupt 5 days before the procedure with parenteral anticoagulant bridging
Moderate
Omit anticoagulant one day before the procedure
Reinitiate anticoagulant one day after the procedure
Assess thromboembolic risk:
Low – moderate risk: interrupt 5 days before the procedure without parenteral anticoagulant bridging
High risk: interrupt 5 days before the procedure with parenteral anticoagulant bridging
Reinitiate warfarin postoperatively once hemostasis is attained
High
Omit anticoagulant two day before the procedure
Reinitiate anticoagulant two day after the procedure
For individuals receiving dabigatran with CrCl 30 to 50 mL/min: omit four days before procedure
interrupt 5 days before the procedure with parenteral anticoagulant bridging
Reinitiate warfarin postoperatively once hemostasis is attained
Table 3.
Periprocedural management of anticoagulants.
On the other side, patients who are on warfarin and undergoing minimal risk procedures, interruption of anticoagulation is not necessary. However, in other low and moderate risk procedures, warfarin should be interrupted with mostly no need for bridging. In high risk, interruption of anticoagulation is needed with bridging. Discontinuation of warfarin should be done five days before the procedure. When bridging is required, starting enoxaparin three days before the procedure is reasonable with last dose being given 24 hours before the procedure. In patients with various degrees of renal impairments may require longer interruption periods as clearance of the anticoagulant may become delayed. Table 3 summarizes the periprocedural management of anticoagulants.
4. Reversal Agents
4.1 Warfarin reversal modalities
Holding or discontinuing warfarin as a solo strategy may be adequate in asymptomatic patients with an elevated INR value and a low risk for bleeding. Certain patient may require further agents to be administered such as, Vitamin K (phytonadione), Prothrombin Complex Concentrate (PCC), and Fresh frozen plasma (FFP) [15].
4.1.1 Vitamin K (Phytonadione)
Exogenous vitamin K level helps reestablishing the hepatic formation of vitamin K–dependent clotting factors. When exogenous vitamin K is given, it can continue to be reduced and converted to its active form, KH2, which results with functional clotting factors despite recent warfarin administration. Vitamin K dose and route of administration vary depends on the bleeding magnitude. It can be given as 2–5 mg PO/IV for minor bleeding events and 5–10 IV for major bleed. Although they are rare, anaphylactic reactions and temporary warfarin resistance have been reported with vitamin K use IV vitamin K normalizes the INR quicker than PO. It only takes 8–12 hours with IV administration and might take up to 24–48 hours following oral administration [15].
4.1.2 Prothrombin Complex Concentrate (PCC)
Clotting factor replenishing, and it can enchase platelet activation. These clotting factors are 25-fold more concentrated than blood. Recombinant activated factor VII (FVIIa) (NovoSeven®) contains activated factor VII can directly activate thrombin generation by binding to tissue factor. PCC products are differentiated by the type of clotting factors they consist of. The 3-factor PCC consist of clotting factors II, IX, and X. The 4-factor PCC 4 consist of clotting factors II, IX, X, and VII (4PCC). Activated 4-factor PCC consist of II, IX, X, and VIIa. All PCC products have natural anticoagulants protein C and protein S. and all PCC products contain heparin, except Profilnine® (3-factor PCC)[15].
PCC dosing is based on factor IX and activated versus non-activated pertains to factor VII. Normally each single-dose vial of PCC is mixed with 10–40 mL of sterile water. Fixed dose PCC for non-intracranial hemorrhagic (ICH) bleed is usually 1000 units while in ICH, it is 1500–2000 units. The other modality to dose PCC is INR and weight driven dose. In patients with INR of 2 to less than 4, the dose is 25 units/kg. In patients with INR of 4–6, the dose is 35 units/kg. In patients with INR of more than 6, the dose is 50 units/kg. PCC dose might need to be rounded up or down to the nearest available vial size. The acceptable dose adjusting margin is institution dependent (usually 5–10%). Infusion related allergic reactions, heparin-induced thrombocytopenia (with exception of Profilnine®) and low acceptable risk of thrombosis have been reported in patients receiving PCC therapy [15].
4.1.3 Fresh frozen plasma (FFP)
FFP is not a specific reversal agent. It contains all coagulation factors, including II, VII, IX, and X in diluted inactive form. Moreover, it contains fibrinogen and platelet. There is no specific recommendation when it comes to FFP dosing, but usually it is given as 10–30 mL/kg (1-unit FFP has a volume of 250 mL). Transfusion reactions, volume overload, infection, and transfusion-related lung injury have been reported in patients receiving FFP therapy [15].
4.2 Direct thrombin inhibitors reversal agents
4.2.1 Idarucizumab
Idarucizumab is a humanized monoclonal antibody fragment that has been developed specifically to reverse the anticoagulation effect of dabigatran [9]. Idarucizumab is indicated for emergent surgery/urgent procedures In life-threatening or uncontrolled bleeding. It is given as a total dose of 5 grams (two separate doses of 2.5 g diluted in 50 mL vials) intravenous infusion over 5 minutes. Idarucizumab carries a warning for inducing thromboembolic events. The thrombotic rate in REVERSE-AD trial was 4.8% at 1 month. The risks of hypersensitivity and severe adverse reactions in patients with hereditary fructose intolerance are reported in the packaging insert due to sorbitol excipient. Among patients who received Idarucizumab, 5% or more experienced hypokalemia, pneumonia, pyrexia, and delirium [9].
4.2.2 Prothrombin Complex Concentrates (PCC)
Inconsistent data was reported regarding the efficacy of PCC in reversing dabigatran based on its laboratory abnormalities. When PCC is used, aPCC such as FEIBA may be preferred. The thrombin generation following PCC administration is dose dependent. Currently most guidelines recommend aPCC 50 units/kg to be given when an emergent reversal is needed for dabigatran. Because of the presence of activated clotting factors, and higher prothrombin and thrombin content in aPCC, the risk of thrombosis is expected to be higher with aPCC than with PCC [9].
4.3 Anti-Xa inhibitors reversal agents
4.3.1 Andexanet alfa
Andexanet alpha is a recombinant modified human “decoy” factor Xa protein, and it works through a competitive binding mechanism with high specificity to direct and indirect anti-Xa agents; to restore the activity of factor Xa and reverses the anticoagulant effect. In May 2018, the FDA approved Andexxa® for the reversal of apixaban and rivaroxaban in the setting of life-threatening or uncontrolled major bleeding. Later, the European Medicine Agency (EMA) gave it a ‘conditional authorization’ in 2019 using the trade name of (Ondexxya®)[9].
Andexanet alpha dosing is either 400 mg IV bolus followed by continuous IV infusion or 800 mg IV bolus followed by 960 mg continuous IV infusion, based on drug, dose, and timing. Treatment with the high dose would cost $49,500 for the drug alone. It is available as 100-mg dry powder vials. It needs to be reconstituted with 10 mL SWFI with typical dissolution time of 3 minutes. Most common reported issues related to andexanet alfa include flushing and fever which may be an infusion related side effect in study performed in healthy volunteers. Albeit the decoy mechanism of action of this drug, the most common side effects in patients with major bleeding events were thromboembolism including DVTs, myocardial infarction and ischemic stroke which was reported in 10% in the ANEXXA-4 trial.
4.3.2 Prothrombin Complex Concentrates (PCCs)
Variable data have been reported on the role of PCC in anti-Xa as potential reversal strategies. Multiple guidelines suggest using PCCs as alternative method to andexanet alfa. However, multiple reports demonstrated similar efficacy and safety profile for PCCs when used for major bleed induced by rivaroxaban, apixaban, or edoxaban. Many clinicians may prefer PCCs over andexanet alfa based on the cost difference in addition to the lack of high-quality head-to-head comparisons. Dosing may have a range between 25 and 50 units/kg based on actual body weight [9].
5. Ongoing research on anticoagulant therapy
The anti-factor Xa inhibitors have achieved so many milestones and currently are recommended by most well-respected clinical guidelines. This mechanism of action is becoming so appealing for many manufacturers to design new agents that specifically target factor Xa. Darexaban and nokxaban are two new potential agents that may see the light soon and attain the guidelines recommendations for many clinical indications. They have still not been approved by neither the US FDA nor the EMA but their Phase II trials are promising with comparable safety and efficacy data to current approved DOACs. On the other side, currently approved DOACs are being tested for many other indications and we may see further utilization of these agents on a wider range of patient population. Drugs targeting other coagulation factors such as factor XI and XII are also being developed [16, 17, 18, 19].
6. Conclusion
Several anticoagulant agents could be used to manage thrombotic events. However, it is essential to consider thrombectomy over anticoagulant therapy in acute settings. This is mainly due to the fact that limited data exist on the use of VKA or DOACs in the acute treatment of patients with ischemic stroke. Anticoagulants could be reserved as a secondary prevention strategy in many thrombotic disorders.
Conf lict of interest
The authors declare no conflict of interest.
Notes/thanks/other declarations
None.
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Introduction",level:"1"},{id:"sec_2",title:"2. Vitamin K Antagonists",level:"1"},{id:"sec_2_2",title:"2.1 Mechanism of action",level:"2"},{id:"sec_3_2",title:"2.2 Pharmacology",level:"2"},{id:"sec_4_2",title:"2.3 Indication and dosing",level:"2"},{id:"sec_5_2",title:"2.4 Monitoring",level:"2"},{id:"sec_6_2",title:"2.5 Side effects",level:"2"},{id:"sec_7_2",title:"2.6 Drug interaction",level:"2"},{id:"sec_9",title:"3. Direct Oral Anticoagulants",level:"1"},{id:"sec_9_2",title:"3.1 Mechanism of action",level:"2"},{id:"sec_10_2",title:"3.2 Pharmacology",level:"2"},{id:"sec_11_2",title:"3.3 Indications and dosing",level:"2"},{id:"sec_12_2",title:"3.4 Monitoring",level:"2"},{id:"sec_13_2",title:"3.5 Side effects",level:"2"},{id:"sec_14_2",title:"3.6 Choosing an anticoagulant agent",level:"2"},{id:"sec_15_2",title:"3.7 Periprocedural management of anticoagulation",level:"2"},{id:"sec_17",title:"4. Reversal Agents",level:"1"},{id:"sec_17_2",title:"4.1 Warfarin reversal modalities",level:"2"},{id:"sec_17_3",title:"4.1.1 Vitamin K (Phytonadione)",level:"3"},{id:"sec_18_3",title:"4.1.2 Prothrombin Complex Concentrate (PCC)",level:"3"},{id:"sec_19_3",title:"4.1.3 Fresh frozen plasma (FFP)",level:"3"},{id:"sec_21_2",title:"4.2 Direct thrombin inhibitors reversal agents",level:"2"},{id:"sec_21_3",title:"4.2.1 Idarucizumab",level:"3"},{id:"sec_22_3",title:"4.2.2 Prothrombin Complex Concentrates (PCC)",level:"3"},{id:"sec_24_2",title:"4.3 Anti-Xa inhibitors reversal agents",level:"2"},{id:"sec_24_3",title:"4.3.1 Andexanet alfa",level:"3"},{id:"sec_25_3",title:"4.3.2 Prothrombin Complex Concentrates (PCCs)",level:"3"},{id:"sec_28",title:"5. Ongoing research on anticoagulant therapy",level:"1"},{id:"sec_29",title:"6. Conclusion",level:"1"},{id:"sec_30",title:"Conf lict of interest",level:"1"},{id:"sec_31",title:"Notes/thanks/other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Dahlbäck B. Blood coagulation. Lancet. 2000;355(9215):1627-1632.'},{id:"B2",body:'Lim GB. Milestone 1: Discovery and purification of heparin. Nat Rev Cardiol. 2017 Dec 14.'},{id:"B3",body:'Lim GB. Milestone 2: Warfarin: from rat poison to clinical use. Nat Rev Cardiol. 2017 Dec 14.'},{id:"B4",body:'Cully M. Milestone 9: Ximelagatran sets the stage for NOACs. Nat Rev Cardiol. 2017 Dec 14.'},{id:"B5",body:'Huynh K. Milestone 10: Era of the NOACs. Nat Rev Cardiol. 2017 Dec 14.'},{id:"B6",body:'Harter K, Levine M, Henderson SO. Anticoagulation drug therapy: a review. West J Emerg Med. 2015 Jan;16(1):11-17.'},{id:"B7",body:'Badreldin H, Nichols H, Rimsans J, Carter D. Evaluation of anticoagulation selection for acute venous thromboembolism. J Thromb Thrombolysis. 2017 Jan;43(1):74-78.'},{id:"B8",body:'Weitz JI. Factor Xa and thrombin as targets for new oral anticoagulants. Thromb Res. 2011 Jan;127 Suppl:S5-12.'},{id:"B9",body:'Chaudhary R, Sharma T, Garg J, Sukhi A, Bliden K, Tantry U, et al. Direct oral anticoagulants: a review on the current role and scope of reversal agents. J Thromb Thrombolysis. 2020 Feb;49(2):271-286.'},{id:"B10",body:'Connors JM. Testing and monitoring direct oral anticoagulants. Blood. 2018;132(19):2009-2015.'},{id:"B11",body:'Wadsworth D, Sullivan E, Jacky T, Sprague T, Feinman H, Kim J. A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant. 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Clinical pharmacokinetics, pharmacodynamics, safety and tolerability of darexaban, an oral direct factor Xa inhibitor, in healthy Caucasian and Japanese subjects. Biopharm Drug Dispos. 2013 Nov;34(8):431-441.'},{id:"B18",body:'Choi HY, Choi S, Kim YH, Lim HS. Population Pharmacokinetic and Pharmacodynamic Modeling Analysis of GCC-4401C, a Novel Direct Factor Xa Inhibitor, in Healthy Volunteers. CPT pharmacometrics Syst Pharmacol. 2016;5(10):532-543.'},{id:"B19",body:'Weitz JI, Chan NC. Advances in Antithrombotic Therapy. Arterioscler Thromb Vasc Biol. 2019;39(1):7-12.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Mohammed Aldhaeefi",address:null,affiliation:'
Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
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The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"46296",doi:"10.5772/57398",title:"Physiological Role of Amyloid Beta in Neural Cells: The Cellular Trophic Activity",slug:"physiological-role-of-amyloid-beta-in-neural-cells-the-cellular-trophic-activity",totalDownloads:5907,totalCrossrefCites:19,totalDimensionsCites:32,abstract:null,book:{id:"3846",slug:"neurochemistry",title:"Neurochemistry",fullTitle:"Neurochemistry"},signatures:"M. del C. Cárdenas-Aguayo, M. del C. Silva-Lucero, M. Cortes-Ortiz,\nB. Jiménez-Ramos, L. 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Luna-Muñoz and M.A.\nMeraz-Ríos",authors:[{id:"42225",title:"Dr.",name:"Jose",middleName:null,surname:"Luna-Muñoz",slug:"jose-luna-munoz",fullName:"Jose Luna-Muñoz"},{id:"114746",title:"Dr.",name:"Marco",middleName:null,surname:"Meraz-Ríos",slug:"marco-meraz-rios",fullName:"Marco Meraz-Ríos"},{id:"169616",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Cardenas-Aguayo",slug:"maria-del-carmen-cardenas-aguayo",fullName:"Maria del Carmen Cardenas-Aguayo"},{id:"169857",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Silva-Lucero",slug:"maria-del-carmen-silva-lucero",fullName:"Maria del Carmen Silva-Lucero"},{id:"169858",title:"Dr.",name:"Maribel",middleName:null,surname:"Cortes-Ortiz",slug:"maribel-cortes-ortiz",fullName:"Maribel Cortes-Ortiz"},{id:"169859",title:"Dr.",name:"Berenice",middleName:null,surname:"Jimenez-Ramos",slug:"berenice-jimenez-ramos",fullName:"Berenice Jimenez-Ramos"},{id:"169860",title:"Dr.",name:"Laura",middleName:null,surname:"Gomez-Virgilio",slug:"laura-gomez-virgilio",fullName:"Laura Gomez-Virgilio"},{id:"169861",title:"Dr.",name:"Gerardo",middleName:null,surname:"Ramirez-Rodriguez",slug:"gerardo-ramirez-rodriguez",fullName:"Gerardo Ramirez-Rodriguez"},{id:"169862",title:"Dr.",name:"Eduardo",middleName:null,surname:"Vera-Arroyo",slug:"eduardo-vera-arroyo",fullName:"Eduardo Vera-Arroyo"},{id:"169863",title:"Dr.",name:"Rosana Sofia",middleName:null,surname:"Fiorentino-Perez",slug:"rosana-sofia-fiorentino-perez",fullName:"Rosana Sofia Fiorentino-Perez"},{id:"169864",title:"Dr.",name:"Ubaldo",middleName:null,surname:"Garcia",slug:"ubaldo-garcia",fullName:"Ubaldo Garcia"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9707,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"26258",doi:"10.5772/28300",title:"Excitotoxicity and Oxidative Stress in Acute Ischemic Stroke",slug:"excitotoxicity-and-oxidative-stress-in-acute-ischemic-stroke",totalDownloads:7183,totalCrossrefCites:6,totalDimensionsCites:25,abstract:null,book:{id:"931",slug:"acute-ischemic-stroke",title:"Acute Ischemic Stroke",fullTitle:"Acute Ischemic Stroke"},signatures:"Ramón Rama Bretón and Julio César García Rodríguez",authors:[{id:"73430",title:"Prof.",name:"Ramon",middleName:null,surname:"Rama",slug:"ramon-rama",fullName:"Ramon Rama"},{id:"124643",title:"Prof.",name:"Julio Cesar",middleName:null,surname:"García",slug:"julio-cesar-garcia",fullName:"Julio Cesar García"}]},{id:"62072",doi:"10.5772/intechopen.78695",title:"Brain-Computer Interface and Motor Imagery Training: The Role of Visual Feedback and Embodiment",slug:"brain-computer-interface-and-motor-imagery-training-the-role-of-visual-feedback-and-embodiment",totalDownloads:1455,totalCrossrefCites:13,totalDimensionsCites:24,abstract:"Controlling a brain-computer interface (BCI) is a difficult task that requires extensive training. Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192987,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]},{id:"63258",title:"Anatomy and Function of the Hypothalamus",slug:"anatomy-and-function-of-the-hypothalamus",totalDownloads:4596,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"The hypothalamus is a small but important area of the brain formed by various nucleus and nervous fibers. Through its neuronal connections, it is involved in many complex functions of the organism such as vegetative system control, homeostasis of the organism, thermoregulation, and also in adjusting the emotional behavior. The hypothalamus is involved in different daily activities like eating or drinking, in the control of the body’s temperature and energy maintenance, and in the process of memorizing. It also modulates the endocrine system through its connections with the pituitary gland. Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3523,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3609,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1349,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82319",title:"Traumatic Optic Neuropathy",slug:"traumatic-optic-neuropathy",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.104731",abstract:"Traumatic optic neuropathy (TON) is a specific neurological sequence of traumatic brain injury (TBI). It has a different mechanism than other most neurologic complications of head trauma and its consequences can be devastating. The damage can be from direct penetrating trauma or bone fracture injuring the optic nerve directly or secondary to indirect blunt trauma (usually causing traction). The diagnosis of TON is based on the clinical history and examination findings indicative of optic neuropathy, especially the presence of defective pupillary light response. TON can cause only mild vision loss but, in some cases, severe vision loss is present. Imaging findings can support the diagnosis, and provide information on the mechanism as well as treatment options. The treatment options include observation alone, systemic steroids, erythropoietin, surgical decompression of the optic canal, or combination. The evidence base for these various treatment options is controversial and each treatment has its side effects and risks. Poor prognostic factors include poor visual acuity at presentation, loss of consciousness, no improvement in vision in the first 48 hours, and evidence of optic canal fractures on neuroimaging.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Ainat Klein and Wahbi Wahbi"},{id:"82203",title:"Resting-State Brain Network Analysis Methods and Applications",slug:"resting-state-brain-network-analysis-methods-and-applications",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.104827",abstract:"Resting-state fMRI has been widely applied in clinical research. Brain networks constructed by functional connectivity can reveal alterations related to disease and treatment. One of the major concerns of brain network application under clinical situations is how to analyze groups of data to find the potential biomarkers that can aid in diagnosis. In this paper, we briefly review common methods to construct brain networks from resting-state fMRI data, including different ways of the node definition and edge calculation. We focus on using a brain atlas to define nodes and estimate edges by static and dynamic functional connectivity. The directed connectivity method is also mentioned. We then discuss the challenges and pitfalls when analyzing groups of brain networks, including functional connectivity alterations, graph theory attributes analysis, and network-based statistics. Finally, we review the clinical application of resting-state fMRI in neurorehabilitation of spinal cord injury patients and stroke patients, the research on the mechanism and early diagnosis of neurodegenerative diseases, such as multiple system atrophy, as well as the research on brain functional network alteration of glioma patients.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Yunxiang Ge and Weibei Dou"},{id:"82099",title:"Recent Advances in the Development of Biofluid-Based Prognostic Biomarkers of Diffuse Axonal Injury",slug:"recent-advances-in-the-development-of-biofluid-based-prognostic-biomarkers-of-diffuse-axonal-injury",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104933",abstract:"Even though head injury is a silent pandemic of the century producing immense social and economic impact, predictive models have not been established to develop strategies promoting the development of reliable diagnostic tools and effective therapeutics capable of improving the prognosis. Diffuse axonal injury (DAI) is a type of traumatic brain injury (TBI) that results from a blunt injury to the brain. Discovering biomarkers for DAI have been a matter of debate and research. A number of studies have reported biomarkers that are correlated with severity of TBI but no conclusive and reproducible clinical evidence regarding the same has been put forward till now. Additionally, many DAI biomarkers have limitations so that they cannot be generalized for universal applications. The properties of these biomarkers should be extensively researched along with the development of novel biomarkers to aid important clinical decisions for the benefit of the society. This chapter summarizes the existing biofluid-based biomarkers, critically examines their limitations and highlights the possibilities of a few novel biomolecules as prognostic biomarkers of DAI.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Vinu V. Gopal, Rinku Raj Mullasseril and Goutam Chandra"},{id:"81998",title:"Understanding the Neuropathophysiology of Psychiatry Disorder Using Transcranial Magnetic Stimulation",slug:"understanding-the-neuropathophysiology-of-psychiatry-disorder-using-transcranial-magnetic-stimulatio",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.103748",abstract:"Transcranial magnetic stimulation (TMS) is a safe and non-invasive tool that allows researchers to probe and modulate intracortical circuits. The most important aspect of TMS is its ability to directly stimulate the cortical neurons, generating action potentials, without much effect on intervening tissue. This property can be leveraged to provide insight into the pathophysiology of various neuropsychiatric disorders. Using multiple patterns of stimulations (single, paired, or repetitive), different neurophysiological parameters can be elicited. Various TMS protocol helps in understanding the neurobiological basis of disorder and specific behaviors by allowing direct probing of the cortical areas and their interconnected networks. While single-pulse TMS can provide insight into the excitability and integrity of the corticospinal tract, paired-pulse TMS (ppTMS) can provide further insight into cortico-cortical connections and repetitive TMS (rTMS) into cortical mapping and modulating plasticity.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Jitender Jakhar, Manish Sarkar and Nand Kumar"},{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:30,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"}],onlineFirstChaptersTotal:13},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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